Summary
Serine deficiency disorders are rare defects in the biosynthesis of the amino acid L-serine. At present two disorders have been reported: 3-phosphoglycerate dehydrogenase deficiency and 3-phosphoserine phosphatase deficiency. These enzyme defects lead to severe neurological symptoms such as congenital microcephaly and severe psychomotor retardation and in addition in patients with 3-phosphoglycerate dehydrogenase deficiency to intractable seizures. These symptoms respond to a variable degree to treatment with L-serine, sometimes combined with glycine. In this paper the current practice of amino acid treatment with L-serine and glycine in serine deficiency is reviewed.
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Abbreviations
- 5,10-MTHF:
-
5,10-methylenetetrahydrofolate
- 5-MTHF:
-
5-methyltetrahydrofolate
- NMDA:
-
N-methyl-d-aspartate
- 3-PGDH:
-
3-phosphoglycerate dehydrogenase
- 3-PSP:
-
3-phosphoserine phosphatase
References
Colombaioni L, Garcia-Gil M (2004) Sphingolipid metabolites in neural signalling and function. Brain Res Rev 46: 328–355.
de Koning TJ, Klomp LWJ (2004) Serine deficiency syndromes. Curr Opin Neurol 17: 197–204.
de Koning TJ, Duran M, Dorland L, et al (1998) Beneficial effects of l-serine and glycine in the management of seizures in 3-phosphoglycerate dehydrogenase deficiency. Ann Neurol 44: 261–265.
de Koning TJ, Jaeken J, Pineda M, Van Maldergem L, Poll-The BT, van der Knaap MS (2000) Hypomyelination and reversible white matter attenuation in 3-phosphoglycerate dehydrogenase deficiency. Neuropediatrics 31: 287–292.
de Koning TJ, Duran M, Van Maldergem L, et al (2002) Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. J Inherit Metab Dis 25: 119–125.
de Koning TJ, Klomp LWJ, van Oppen C, et al (2004) Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency. Lancet 364: 2221–2222.
Hausler MG, Jaeken J, Monch E, Ramaekers VT (2001) Phenotypic heterogeneity and adverse effects of serine treatment in 3-phosphoglycerate dehydrogenase deficiency: report on two siblings. Neuropediatrics 32: 191–195.
Jaeken J, Detheux M, Van Maldergem L, Foulon M, Carchon H, Van Schaftingen E (1996) 3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis. Arch Dis Child 74: 542–545.
Jaeken J, Detheux M, Fryns JP, Collet JF, Alliet P, Van Schaftingen E (1997) Phosphoserine phosphatase deficiency in a patient with Williams syndrome. J Med Genet 34: 594–596.
Klomp LW, de Koning TJ, Malingre HE, et al (2000) Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency—a neurometabolic disorder associated with reduced l-serine biosynthesis. Am J Hum Genet 67: 1389–1399.
Luberto C, Kraveka JM, Hannun YA (2002) Ceramide regulation of apoptosis versus differentiation: a walk on a fine line. Lessons from neurobiology. Neurochem Res 27: 609–617.
Mothet JP, Parent AT, Wolosker H, et al (2000) d-Serine is an endogenous ligand for the glycine site of the N-methyl-d-aspartate receptor. Proc Natl Acad Sci USA 97: 4926–4931.
Pineda M, Vilaseca MA, Artuch R, et al (2000) 3-Phosphoglycerate dehydrogenase deficiency in a patient with West syndrome. Dev Med Child Neurol 42: 629–633.
Pind S, Slominski E, Mauthe J, et al (2002) V490M, a common mutation in 3-phosphoglycerate dehydrogenase deficiency, causes enzyme deficiency by decreasing the yield of mature enzyme. J Biol Chem 277: 7136–7143.
Ramaekers VT, Rothenberg SP, Sequeira JM, et al (2005) Autoantibodies to folate receptors in the cerebral folate deficiency syndrome. N Engl J Med 352: 1985–1991.
Smith QR, Momma S, Aoyagi M, Rapoport SI (1987) Kinetics of neutral amino acid transport across the blood–brain barrier. J Neurochem 49: 1651–1658.
Snell K (1984) Enzymes of serine metabolism in normal, developing and neoplastic rat tissues. Adv Enzyme Regul 22: 325–400.
TyurinaYY, Shvedova AA, Kawai K, et al (2000) Phospholipid signaling in apoptosis: peroxidation and externalization of phosphatidylserine. Toxicology 148: 93–101.
Veiga-da-Cunha M, Collet JF, Prieur B, et al (2004) Mutations responsible for 3-phosphoserine phosphatase deficiency. Eur J Hum Genet 12: 163–166.
Xia M, Liu Y, Figueroa DJ, et al (2004) Characterization and localization of a human serine racemase. Brain Res Mol Brain Res 125: 96–104.
Yoshida K, Furuya S, Osuka, S, et al (2004) Targeted disruption of the mouse 3-phosphoglycerate dehydrogenase gene causes severe neurodevelopmental defects and results in embryonic lethality. J Biol Chem 279: 3573–3577.
Zwaal RFA, Comfurius P, Bevers EM (2004) Scott syndrome, a bleeding disorder caused by defective scrambling of membrane phospholipids. Biochim Biophys Acta 1636: 119–128.
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Communicating editor: Jean-Marie Saudubray
Competing interests: None declared
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de Koning, T.J. Treatment with amino acids in serine deficiency disorders. J Inherit Metab Dis 29, 347–351 (2006). https://doi.org/10.1007/s10545-006-0269-0
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DOI: https://doi.org/10.1007/s10545-006-0269-0